- Novel cobalt-valine catalyzed O-arylation of phenols with electron deficient aryl iodides
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Abstract: A Novel cobalt-catalyzed O-arylation of phenols with electron deficient aryl iodides is described. The reaction employs cheap and easy-to-handle cobalt acetate tetrahydrate as the catalyst precursor and naturally occurring l-valine as the ligand without the use of any transmetallating or reducing agents. The new protocol offers a wide scope for a variety of phenols towards O-arylation with moderate to excellent yields with electron deficient aryl iodides.
- Ujwaldev, Sankuviruthiyil M.,Saranya, Salim,Harry, Nissy Ann,Anilkumar, Gopinathan
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Read Online
- Ullmann Coupling Reaction of Nitro-Substituted Aryl Halides with Phenols under Mild Conditions: Micro-/Mesoporous Hierarchical LaAlPO-5 Zeolite Catalyst
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Heterogeneous catalytic reactions of aromatic organic molecules over zeolite catalysts present many challenges because of the shape selectivity of the micropores of conventional zeolites that limits the diffusion of aromatic molecules. Herein, Ullmann coupling reactions of phenols with nitro-substituted aryl halides were catalyzed by rare-earth-doped mesoporous AlPO-5 zeolites in the absence of ligands. The AlPO-5-MAlPO-5-M zeolites had a pure AFI structure and consisted of spherical particles assembled by nanofibers. The rare-earth elements were highly dispersed in the AlPO-5-MAlPO-5-M samples. The LaAlPO-5-MAlPO-5-M zeolite is an excellent catalyst for Ullmann coupling reactions of phenols and nitro-substituted aryl halides. Mesoporous LaAlPO-5 has an excellent stability and recyclability in the Ullmann coupling of p-X-nitrobenzene (X=Cl, Br, and I) with 2-naphthol. These results are important in the exploration of attractive Ullmann coupling reactions and in the development of mesoporous zeolite catalysts for other organic reactions.
- Ke, Qingping,Wu, Mingzhou,Wang, Chao,Lu, Guanzhong
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Read Online
- Salicylanilides Reduce SARS-CoV-2 Replication and Suppress Induction of Inflammatory Cytokines in a Rodent Model
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SARS-CoV-2 virus has recently given rise to the current COVID-19 pandemic where infected individuals can range from being asymptomatic, yet highly contagious, to dying from acute respiratory distress syndrome. Although the world has mobilized to create antiviral vaccines and therapeutics to combat the scourge, their long-term efficacy remains in question especially with the emergence of new variants. In this work, we exploit a class of compounds that has previously shown success against various viruses. A salicylanilide library was first screened in a SARS-CoV-2 activity assay in Vero cells. The most efficacious derivative was further evaluated in a prophylactic mouse model of SARS-CoV-2 infection unveiling a salicylanilide that can reduce viral loads, modulate key cytokines, and mitigate severe weight loss involved in COVID-19 infections. The combination of anti-SARS-CoV-2 activity, cytokine inhibitory activity, and a previously established favorable pharmacokinetic profile for the lead salicylanilide renders salicylanilides in general as promising therapeutics for COVID-19.
- Beutler, Nathan,Blake, Steven,Eubanks, Lisa M.,Janda, Kim D.,Ji, Henry,Manning, John T.,Maruyama, Junki,Paessler, Slobodan,Shaabani, Namir,Teijaro, John R.
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p. 2229 - 2237
(2021/08/24)
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- CoII Immobilized on Aminated Magnetic-Based Metal–Organic Framework: An Efficient Heterogeneous Nanostructured Catalyst for the C–O Cross-Coupling Reaction in Solvent-Free Conditions
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Abstract: In this paper, we report the synthesis of Fe3O4?AMCA-MIL53(Al)-NH2-CoII NPs based on the metal–organic framework structures as a magnetically separable and environmentally friendly heterogeneous nanocatalyst. The prepared nanostructured catalyst efficiently promotes the C–O cross-coupling reaction in solvent-free conditions without the need for using toxic solvents and/or expensive palladium catalyst. Graphic Abstract: [Figure not available: see fulltext.].
- Mohammadinezhad, Arezou,Akhlaghinia, Batool
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p. 332 - 352
(2020/01/11)
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- Salicylanilide Analog Minimizes Relapse of Clostridioides difficile Infection in Mice
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Clostridioides difficile infection (CDI) causes serious and sometimes fatal symptoms like diarrhea and pseudomembranous colitis. Although antibiotics for CDI exist, they are either expensive or cause recurrence of the infection due to their altering the colonic microbiota, which is necessary to suppress the infection. Here, we leverage a class of known membrane-targeting compounds that we previously showed to have broad inhibitory activity across multiple Clostridioides difficile strains while preserving the microbiome to develop an efficacious agent. A new series of salicylanilides was synthesized, and the most potent analog was selected through an in vitro inhibitory assay to evaluate its pharmacokinetic parameters and potency in a CDI mouse model. The results revealed reduced recurrence of CDI and diminished disturbance of the microbiota in mice compared to standard-of-care vancomycin, thus paving the way for novel therapy that can potentially target the cell membrane of C. difficile to minimize relapse in the recovering patient.
- Blake, Steven,Thanissery, Rajani,Rivera, Alissa J.,Hixon, Mark S.,Lin, Mingliang,Theriot, Casey M.,Janda, Kim D.
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p. 6898 - 6908
(2020/07/28)
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- A new strategy to design a graphene oxide supported palladium complex as a new heterogeneous nanocatalyst and application in carbon–carbon and carbon-heteroatom cross-coupling reactions
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The palladium nanoparticles were successfully stabilized with an average diameter of 6–7?nm through the coordination of palladium and terpyridine-based ligands grafted on graphene oxide surface. The graphene oxide supported palladium nanoparticles were thoroughly characterized and applied as an efficient heterogeneous catalyst in carbon–carbon (Suzuki-Miyaura, Mizoroki-Heck coupling reactions) and carbon–heteroatom (C-N and C-O) bond-forming reactions. The catalyst was simply recycled from the reaction mixture and was reused consecutive four times with small drop in catalytic activity.
- Bahrami, Kiumars,Targhan, Homa
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- Cu(I)-PNF, an organic-based nanocatalyst, catalyzed C-O and C-S cross-coupling reactions
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Peptide nanofiber has been prepared via a self-assembly protocol and decorated with Cu(I) to prepare a nanostructural catalyst. The catalytic activity of this prepared nanomaterial (Cu(I)-PNF) was examined in C-O and C-S cross-coupling reactions. Compared with conventional copper-ligand catalytic systems, CuNP-PNF has unique advantages such as water solubility, high efficiency, and low cost, which makes it a highly efficient and beneficial catalyst to reuse in cross-coupling reactions.
- Taherinia, Zahra,Ghorbani-Choghamarani, Arash
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- Novel Deazaflavin Analogues Potently Inhibited Tyrosyl DNA Phosphodiesterase 2 (TDP2) and Strongly Sensitized Cancer Cells toward Treatment with Topoisomerase II (TOP2) Poison Etoposide
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Topoisomerase II (TOP2) poisons as anticancer drugs work by trapping TOP2 cleavage complexes (TOP2cc) to generate DNA damage. Repair of such damage by tyrosyl DNA phosphodiesterase 2 (TDP2) could render cancer cells resistant to TOP2 poisons. Inhibiting TDP2, thus, represents an attractive mechanism-based chemosensitization approach. Currently known TDP2 inhibitors lack cellular potency and/or permeability. We report herein two novel subtypes of the deazaflavin TDP2 inhibitor core. By introducing an additional phenyl ring to the N-10 phenyl ring (subtype 11) or to the N-3 site of the deazaflavin scaffold (subtype 12), we have generated novel analogues with considerably improved biochemical potency and/or permeability. Importantly, many analogues of both subtypes, particularly compounds 11a, 11e, 12a, 12b, and 12h, exhibited much stronger cancer cell sensitizing effect than the best previous analogue 4a toward the treatment with etoposide, suggesting that these analogues could serve as effective cellular probes.
- Kankanala, Jayakanth,Ribeiro, Carlos J. A.,Kiselev, Evgeny,Ravji, Azhar,Williams, Jessica,Xie, Jiashu,Aihara, Hideki,Pommier, Yves,Wang, Zhengqiang
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p. 4669 - 4682
(2019/05/17)
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- A green approach for arylation of phenols using iron catalysis in water under aerobic conditions
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The first efficient iron-catalyzed coupling of aryl iodides with phenols was developed exclusively with water as solvent. The reaction is performed with low cost and readily available FeCl3·6H2O and DMEDA catalytic system providing diaryl ethers in good to excellent yields. The effectiveness of this reaction was further revealed by compatibility with a wide range of functional groups. Moreover, the procedure is rendered simple as this transformation is carried out in the presence of air. Thus, the protocol represents a facile, economical and eco-friendly procedure to access diaryl ethers.
- Sindhu, Kallikkakam S.,Ujwaldev, Sankuviruthiyil M.,Keerthi Krishnan,Anilkumar, Gopinathan
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p. 146 - 150
(2017/03/17)
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- Synthesis, SAR and molecular docking study of novel non-β-lactam inhibitors of TEM type β-lactamase
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The novel classes of acylated phenoxyanilide and thiourea compounds were investigated for their ability to inhibit TEM type β-lactamase enzyme. Two compounds 4g and 5c reveal the inhibition potency in micromolar range and show their action by non-covalent binding in the vicinity of the TEM-171 active site. The structure activity relationship around carbon chain length and different substituents in ortho- and para-positions of acylated phenoxyanilide as well as molecular modelling study has been performed.
- Antipin, Roman L.,Beshnova, Daria A.,Petrov, Rostislav A.,Shiryaeva, Anna S.,Andreeva, Irina P.,Grigorenko, Vitaly G.,Rubtsova, Maya Yu.,Majouga, Alexander G.,Lamzin, Victor S.,Egorov, Alexey M.
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supporting information
p. 1588 - 1592
(2017/03/17)
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- Structure-based design of N-substituted 1-hydroxy-4-sulfamoyl-2-naphthoates as selective inhibitors of the Mcl-1 oncoprotein
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Structure-based drug design was utilized to develop novel, 1-hydroxy-2-naphthoate-based small-molecule inhibitors of Mcl-1. Ligand design was driven by exploiting a salt bridge with R263 and interactions with the p2 pocket of the protein. Significantly, target molecules were accessed in just two synthetic steps, suggesting further optimization will require minimal synthetic effort. Molecular modeling using the Site-Identification by Ligand Competitive Saturation (SILCS) approach was used to qualitatively direct ligand design as well as develop quantitative models for inhibitor binding affinity to Mcl-1 and the Bcl-2 relative Bcl-xL as well as for the specificity of binding to the two proteins. Results indicated hydrophobic interactions in the p2 pocket dominated affinity of the most favourable binding ligand (3bl: Ki = 31 nM). Compounds were up to 19-fold selective for Mcl-1 over Bcl-xL. Selectivity of the inhibitors was driven by interactions with the deeper p2 pocket in Mcl-1 versus Bcl-xL. The SILCS-based SAR of the present compounds represents the foundation for the development of Mcl-1 specific inhibitors with the potential to treat a wide range of solid tumours and hematological cancers, including acute myeloid leukemia.
- Lanning, Maryanna E.,Yu, Wenbo,Yap, Jeremy L.,Chauhan, Jay,Chen, Lijia,Whiting, Ellis,Pidugu, Lakshmi S.,Atkinson, Tyler,Bailey, Hala,Li, Willy,Roth, Braden M.,Hynicka, Lauren,Chesko, Kirsty,Toth, Eric A.,Shapiro, Paul,MacKerell, Alexander D.,Wilder, Paul T.,Fletcher, Steven
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p. 273 - 292
(2016/03/22)
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- A highly active and recyclable catalyst for the synthesis of indole and phenyl ether
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A new simple catalytic system consisting of copper-aluminium and hydrotalcite (CuAl-HT) has been developed using a facile one-pot method without harm to the environment. The catalyst was characterized using TEM, XRD and XPS. It could be used as an efficient catalyst for the synthesis of both indole and phenyl ether. As expected, the catalyst afforded high catalytic activity for the selective synthesis of indole via intramolecular dehydrogenative N-heterocyclization of 2-(2-aminophenyl)ethanol. Meanwhile, it also exhibited superior catalytic properties for an Ullmann-type coupling reaction to synthesise phenyl ether from iodobenzene and phenol. The CuAl-HT catalyst showed higher activity than conventional catalysts based on copper and could be recycled several times with stable catalytic activity. This procedure has real economic advantages since no expensive materials were used.
- Qiao, Bo,Zhang, Le,Li, Rong
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p. 93463 - 93469
(2015/11/17)
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- Ultrasound synthesis of diaryl ethers
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2,2-Bis[4-(4-nitroaryl)phenyl]hexafluoropropanes appropriate for the synthesis of monomers were prepared by the reaction of 2,2-bis[4-hydroxyphenyl)hexafluoropropane with 1-chloro-4-nitrobenzenes under ultrasonic activation.
- Begunov,Valyaeva,Belyaev,Dobretsova
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p. 1971 - 1974
(2016/05/11)
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- CsF/clinoptilolite: An efficient solid base in SNAr and copper-catalyzed Ullmann reactions
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CsF/clinoptilolite was found to be an efficient solid base catalyst for both SNAr and Ullmann ether reactions. A general and efficient one-step procedure was developed for the synthesis of biaryl ethers via direct coupling of electron-deficient aryl halides to phenols using CsF/clinoptilolite. The protocol was also applied to electron-rich aryl halides by addition of a catalytic amount of copper oxide nanoparticles. Both SNAr and Ullmann reactions were rapid and provided good to excellent yields.
- Keipour, Hoda,Hosseini, Abolfazl,Afsari, Amir,Oladee, Razieh,Khalilzadeh, Mohammad A.,Ollevier, Thierry
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- Synthesis and biological evaluation of pentanedioic acid derivatives as farnesyltransferase inhibitors
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Structure-based virtual screening of a commercial library identified pentanedioic acid derivatives (6 and 13b) as a kind of novel scaffold farnesyltransferase inhibitors (FTIs). Chemical modifications of the lead compounds, biological assays and analysis of the structure-activity relationships (SAR) were conducted to discover more potent FTIs. Some of them displayed excellent inhibition against FTase, and among them, the most active compound 13n with an IC50 value of 0.0029 μM and SAR analysis might be helpful to the discovery of more potent FTIs. This journal is
- Yang, Liuqing,Liu, Wei,Mei, Hanbing,Zhang, Yuan,Yu, Xiaojuan,Xu, Yufang,Li, Honglin,Huang, Jin,Zhao, Zhenjiang
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supporting information
p. 671 - 676
(2015/04/27)
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- First palladium-catalyzed denitrated coupling reaction of nitroarenes with phenols
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The first palladium-catalyzed protocol for the denitrated coupling reaction of nitroarenes with phenols has been developed, achieving unsymmetrical diaryl ethers in moderate to excellent yields. The cyclopalladated ferrocenylimine (catalyst Ic) exhibited highly catalytic activity for this transformation with low catalyst loading (0.75 mol%) and short reaction time (2 h). The efficiency of this reaction was demonstrated by its compatibility with a range of groups. Moreover, the rigorous exclusion of air or moisture was not required in these transformations. Copyright
- Wang, Hailei,Yu, Ajuan,Cao, Aijuan,Chang, Junbiao,Wu, Yangjie
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p. 611 - 614
(2013/10/21)
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- Facile preparation of unsymmetrical diaryl ethers from unsymmetrical diaryliodonium tosylates and phenols with high regioselectivity
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Unsymmetrical diaryl ethers were efficiently obtained in good yields by the reactions of aryl(4-methoxyphenyl)iodonium tosylates with phenols, and aryl(2,4-dimethoxyphenyl)iodonium tosylates with phenols, in the presence of potassium carbonate in acetonitrile, respectively. The latter iodonium tosylates provided the corresponding unsymmetrical diaryl ethers in good yields with high regioselectivities, together with the quantitative formation of 1-iodo-2,4-dimethoxybenzene. Georg Thieme Verlag Stuttgart New York.
- Kakinuma, Yohji,Moriyama, Katsuhiko,Togo, Hideo
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p. 183 - 188
(2013/02/23)
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- Quinolin-4(1 H)-imines are potent antiplasmodial drugs targeting the liver stage of malaria
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We present a novel series of quinolin-4(1H)-imines as dual-stage antiplasmodials, several-fold more active than primaquine in vitro against Plasmodium berghei liver stage. Among those, compounds 5g and 5k presented low nanomolar IC50 values. The compounds are metabolically stable and modulate several drug targets. These results emphasize the value of quinolin-4(1H)-imines as a new chemotype and their suitable properties for further drug development.
- Rodrigues, Tiago,Da Cruz, Filipa P.,Lafuente-Monasterio, Maria J.,Gon?alves, Daniel,Ressurrei??o, Ana S.,Sitoe, Ana R.,Bronze, Maria R.,Gut, Jiri,Schneider, Gisbert,Mota, Maria M.,Rosenthal, Philip J.,Prude?ncio, Miguel,Gamo, Francisco-Javier,Lopes, Francisca,Moreira, Rui
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supporting information
p. 4811 - 4815
(2013/07/19)
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- ALLOSTERIC MODULATORS OF METABOTROPIC GLUTAMATE RECEPTORS
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Formula (I), and salts thereof, wherein R1, RA2, RA3 and RA4, are defined herein, which have properties for positive allosteric modulation of mGluR-4 receptor sites. Also described are pharmaceutical formulations comprising the compounds of Formula (I) or their salts, and methods of treating Parkinson's disease and related disorders using the same.
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Paragraph 0138
(2013/05/21)
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- ALLOSTERIC MODULATORS OF METABOTROPIC GLUTAMATE RECEPTORS
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Disclosed are compounds of Formula (I), and salts thereof, wherein R1, RA2, RA3 and RA4, are defined herein, which have properties for positive allosteric modulation of mGluR-4 receptor sites. Also described are pharmaceutical formulations comprising the compounds of Formula (I) or their salts, and methods of treating Parkinson's disease and related disorders using the same.
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Paragraph 0137
(2013/05/21)
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- Ligand-free copper-catalyzed O-arylation of nitroarenes with phenols
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The first example of ligand-free copper-catalyzed O-arylation of nitroarenes with phenols was developed, achieving unsymmetrical diaryl ethers in moderate to excellent yields. This arylation proceeded smoothly without promotion of the ligands, and displayed great functional group compatibility. Thus, the method represents a new, facile, and cost-effective approach to access unsymmetrical diaryl ethers.
- Chen, Jiuxi,Wang, Xingyong,Zheng, Xingwang,Ding, Jinchang,Liu, Miaochang,Wu, Huayue
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supporting information
p. 8905 - 8907
(2012/10/29)
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- Ligand-free solid supported palladium(0) nano/microparticles promoted C-O, C-S, and C-N cross coupling reaction
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Ligand-free solid-supported nano and microparticles of Pd(0) (SS-Pd) were used as a heterogeneous catalyst in carbon-heteroatom bond formation reactions. Nitro substituted aryl halides reacted with oxygen, sulfur, and nitrogen nucleophiles to afford the corresponding products in good yields. A one-pot sequential cross coupling and nitro-reduction was also performed using the same SS-Pd catalyst to access amine substituted carbon-heteroatomic molecules. In addition, SS-Pd could be recycled up to seven runs without a significant loss of catalytic activity.
- Bandna,Guha, Nitul Ranjan,Shil, Arun K.,Sharma, Dharminder,Das, Pralay
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supporting information
p. 5318 - 5322
(2012/10/30)
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- The kinetics and mechanisms of aromatic nucleophilic substitution reactions in liquid ammonia
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The rates of aromatic nucleophilic substitution reactions in liquid ammonia are much faster than those in protic solvents indicating that liquid ammonia behaves like a typical dipolar aprotic solvent in its solvent effects on organic reactions. Nitrofluorobenzenes (NFBs) readily undergo solvolysis in liquid ammonia and 2-nitrofluorobenzene is about 30 times more reactive than the 4-substituted isomer. Oxygen nucleophiles, such as alkoxide and phenoxide ions, readily displace fluorine of 4-NFB in liquid ammonia to give the corresponding substitution product with little or no competing solvolysis product. Using the pKa of the substituted phenols in liquid ammonia, the Bronsted βnuc for the reaction of 4-NFB with para-substituted phenoxides is 0.91, indicative of the removal of most of the negative charge on the oxygen anion and complete bond formation in the transition state and therefore suggests that the decomposition of the Meisenheimer σ-intermediate is rate limiting. The aminolysis of 4-NFB occurs without general base catalysis by the amine and the second-order rate constants generate a Bronsted βnuc of 0.36 using either the pKa of aminium ion in acetonitrile or in water, which is also interpreted in terms of rate limiting breakdown of the Meisenheimer σ-intermediate. Nitrobenzene and diazene are formed as unusual products from the reaction between sodium azide and 4-NFB, which may be due to the initially formed 4-nitroazidobenzene decomposing to give a nitrene intermediate, which may then give diazene or be trapped by ammonia to give the unstable hydrazine which then yields nitrobenzene.
- Ji, Pengju,Atherton, John H.,Page, Michael I.
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supporting information; scheme or table
p. 3286 - 3295
(2011/07/07)
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- Nano ceria catalyzed Ullmann type coupling reactions
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Ullmann type intermolecular coupling of aryl halide with hetero-aromatic compounds, such as phenols, amines, and thiophenols are key reactions for the formation of carbon-heteroatom bond in organic synthesis. We report a robust and novel method that provides an efficient and economic route for the synthesis of O, N, and S-arylation via Ullman coupling by using nano cerium oxide (ceria, CeO2). CeO2 is a cheaper catalyst compared to related copper based catalysts. This method provides a wide range of substrate applicability in the case of phenols and amines. Less reactive chlorobenzene substituted with strong electron withdrawing groups such as 4-nitrochlorobenzene and 4-cyanochlorobenzene favor the reaction. This protocol avoids the use of ligand and gives arylated product in satisfactory yields.
- Agawane, Sandeep M.,Nagarkar, Jayashree M.
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experimental part
p. 5220 - 5223
(2011/10/12)
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- Potassium fluoride supported on natural nanoporous zeolite: A new solid base for the synthesis of diaryl ethers
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An efficient and inexpensive synthesis of diaryl ethers has been developed. The process involves the nucleophilic aromatic substitution of electron-deficient aryl halides and phenols and is mediated by potassium fluoride/Clinoptilolite (KF/CP) in dimethyl sulfoxide (DMSO). The approach affords good to excellent yields of the arylated products without the need for additional cation capture. The solid base is also efficient in the Ullmann ether synthesis. A new, inexpensive solid base for the synthesis of diaryl ethers has been developed. Clinoptilolite, a natural zeolite with a high tendency for cation capture, combined with potassium fluoride, provides an efficientsolid base for the deprotonation of phenols in nucleophilic reactions. The same solid base acts as a reliable base for the copper-catalyzed synthesis of diaryl ethers. Copyright
- Khalilzadeh, Mohammad A.,Hosseini, Abolfazl,Pilevar, Afsaneh
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experimental part
p. 1587 - 1592
(2011/04/22)
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- Iron/copper-cocatalyzed ullmann N,O-arylation using FeCl3, CuO, and rac-1,1′-Binaphthyl-2,2′-diol
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We have developed an efficient and inexpensive bimetallic catalyst FeCl3, CuO, and rac-BINOL that could promote N,O-arylation of aliphatic, arylamines, and phenols. The cross-coupling reaction conditions have high tolerance of various functional groups. This versatile and efficient iron/copper-cocatalyst can widely be used in the synthesis of the compounds containing (aryl)C-N or (aryl)C-O(aryl) bond. Georg Thieme Verlag Stuttgart.
- Wang, Zhe,Fu, Hua,Jiang, Yuyang,Zhao, Yufen
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body text
p. 2540 - 2546
(2009/04/12)
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- Copper-catalyzed Ullmann coupling under ligand- and additive- free conditions. Part 1: O-Arylation of phenols with aryl halides
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O-Arylation of a wide variety of substituted phenols and aliphatic alcohols with aryl halides catalyzed by copper iodide under mild ligand and additive free conditions (nBu4NBr, DMF, K3PO4, reflux, 22 h) is accomplished in good to excellent product yields (up to 95%).
- Chang, Joyce Wei Wei,Chee, Sheena,Mak, Shiya,Buranaprasertsuk, Pongchart,Chavasiri, Warinthorn,Chan, Philip Wai Hong
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p. 2018 - 2022
(2008/09/19)
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- Discovery of novel and potent aryl diamines as leukotriene A4 hydrolase inhibitors
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The synthesis and biological evaluation of a series of aryl diamines as inhibitors of LTA4-h inhibitors are described. The optimization which led to the identification of the optimal para-substitution on the diphenyl ether moiety and diamine spacer is discussed. The resulting compounds such as 3l have excellent enzyme and cellular potency as well as desirable pharmacokinetic properties.
- Khim, Seock-Kyu,Bauman, John,Evans, Jarred,Freeman, Beverly,King, Beverly,Kirkland, Thomas,Kochanny, Monica,Lentz, Dao,Liang, Amy,Mendoza, Lisa,Phillips, Gary,Tseng, Jih-Lie,Wei, Robert G.,Ye, Hong,Yu, Limei,Parkinson, John,Guilford, William J.
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scheme or table
p. 3895 - 3898
(2009/04/07)
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- DBU-mediated mild and chemoselective deprotection of aryl silyl ethers and tandem biaryl ether formation
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An efficient method for the selective cleavage of aryl silyl ethers is established using 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). With either 1.0 or 0.10 equivalent of DBU, smooth desilylation of various aryl silyl ethers was accomplished selectively in the presence of alkyl silyl ethers and other base-sensitive groups such as acetate and ester. In addition, direct transformation of aryl silyl ethers into biaryl ethers using a catalytic amount of DBU was possible through tandem desilylation and SNAr reaction with activated aryl fluorides. Georg Thieme Verlag Stuttgart.
- Yeom, Chang-Eun,Kim, Hye Won,Lee, So Young,Kim, B. Moon
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p. 146 - 150
(2008/03/13)
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- Microwave-assisted construction of diaryl ethers directly from arylmethanesulfonates as convenient latent phenols with aryl halides
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The microwave-assisted synthesis of diaryl ethers directly from aryl halides and arylmethanesulfonates, which as latent phenols obviate a deprotection step prior to the SNAr reaction, in the presence of Cs2CO3 is described. The reaction time was very short (6-9-min), and good to excellent yields (53-90%) with the wide substrate scope were achieved without any catalyst. Copyright Taylor & Francis Group, LLC.
- Xu, Hui,Chen, Yang
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p. 2411 - 2420
(2008/02/10)
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- One-pot microwave-assisted tandem deprotection of arylmethanesulfonates / SNAr reaction for K2CO3-mediated C(aryl)-O bond formation
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One-pot microwave-assisted tandem deprotection of arylmethanesulfonates / nucleophilic aromatic substitution reaction (SNAr) with activated aryl halides to synthesize asymmetrical diaryl ethers is described.
- Xu, Hui,Li, Hong-Feng
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p. 1183 - 1186
(2008/10/09)
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- C(aryl)-O bond formation from aryl methanesulfonates via consecutive deprotection and SNAr reactions with aryl halides in an ionic liquid
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An efficient K3PO4-mediated synthesis of unsymmetrical diaryl ethers using the ionic liquid [Bmim]BF4 (1-butyl-3-methylimidazolium tetrafluoroborate) as solvent has been developed. The procedure involves consecutive deprotection of aryl methanesulfonates and a nucleophilic aromatic substitution (SNAr) with activated aryl halides.
- Xu, Hui,Chen, Yang
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p. 861 - 867
(2008/02/05)
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- Immobilization of copper in organic-inorganic hybrid materials: a highly efficient and reusable catalyst for the Ullmann diaryl etherification
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The immobilization of copper in organic-inorganic hybrid materials catalyzing the Ullmann reaction has been described. Phenols reacted with aryl iodides, aryl bromides and aryl chlorides smoothly in the presence of a 3-(2-aminoethylamino)propyl functionalized silica gel immobilized copper catalyst. The protocol involved the use of DMSO as the solvent, and potassium fluoride as the base. The reactions generated the corresponding cross-coupling products in good to excellent yields. Furthermore, the silica-supported copper could be recovered and recycled by a simple filtration of the reaction solution and used for 10 consecutive trials without loss of its reactivity.
- Miao, Tao,Wang, Lei
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- Correlation between molecular dipole moment and centrosymmetry in some crystalline diphenyl ethers
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The presence of a large molecular dipole moment in diphenyl ethers leads unequivocally to a centrosymmetric crystal structure. The Royal Society of Chemistry 2005.
- Dey, Archan,Desiraju, Gautam R.
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p. 2486 - 2488
(2007/10/03)
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- Novel glycine transporter type-2 reuptake inhibitors. Part 1: α-amino acid derivatives
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A variety of α-amino acid derivatives were prepared as glycine transport inhibitors and their ability to block the uptake of [ 14C]-glycine in COS7 cells transfected with human glycine transporter-2 (hGlyT-2) was evaluated. An array of substituents at the chiral center was studied and overall, L-phenylalanine was identified as the preferred amino acid residue. Compounds prepared from L-amino acids were more potent GlyT-2 inhibitors than analogs derived from the corresponding D-amino acids. Introducing an achiral amino acid such as glycine, or incorporating geminal substitution in the α-position, led to a significant reduction in GlyT-2 inhibitory properties.
- Wolin, Ronald L.,Venkatesan, Hariharan,Tang, Liu,Santillán Jr., Alejandro,Barclay, Tristin,Wilson, Sandy,Lee, Doo Hyun,Lovenberg, Timothy W.
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p. 4477 - 4492
(2007/10/03)
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- Phenoxyphenyl sulfone N-formylhydroxylamines (Retrohydroxamates) as potent, selective, orally bioavailable matrix metalloproteinase inhibitors
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A novel series of sulfone N-formylhydroxylamines (retrohydroxamates) have been investigated as matrix metalloproteinases (MMP) inhibitors. The substitution of the ether linkage of ABT-770 (5) with a sulfone group 13a led to a substantial increase in activity against MMP-9 but was accompanied by a loss of selectivity for inhibition of MMP-2 and -9 over MMP-1 and diminished oral exposure. Replacement of the biphenyl P1′ substituent with a phenoxyphenyl group provided compounds that are highly selective for inhibition of MMP-2 and -9 over MMP-1. Optimization of the substituent adjacent to the retrohydroxamate center in this series led to the clinical candidate ABT-518 (6), a.highly potent, selective, orally bioavailable MMP inhibitor that has been shown to significantly inhibit tumor growth in animal cancer models.
- Wada,Holms,Curtin,Dai,Florjancic,Garland,Guo,Heyman,Stacey,Steinman,Albert,Bouska,Elmore,Goodfellow,Marcotte,Tapang,Morgan,Michaelides,Davidsen
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p. 219 - 232
(2007/10/03)
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- CsF-Al2O3 mediated rapid condensation of phenols with aryl halides: Comparative study of conventional heating vs. microwave irradiation
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Biaryl ethers and thio ethers are formed in high yields by the condensation of phenols and thiophenols with electron-deficient aryl halides using CsF supported on Al2O3 under microwave irradiation in solvent-free conditions.
- Yadav, Jhillu S.,Subba Reddy, Basi V.
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p. 489 - 491
(2007/10/03)
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- Polymer supported bases in combinatorial chemistry: Synthesis of aryl ethers from phenols and alkyl halides and aryl halides
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Polymer supported 1,5,7-triazabicyclo[4.4.0]dec-5-ene (PTBD) was used as a base and a reagent scavenger for rapid synthesis of aryl ethers from phenols and alkyl or aryl halides. This method provides a simple reaction operation, and generally high purity of reaction product in good yield.
- Xu, Wei,Mohan, Raju,Morrissey, Michael M.
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p. 7337 - 7340
(2007/10/03)
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- Process for preparing nitrodiphenyl (thio) ethers
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Nitrodiphenyl(thio) ethers in which the nitro group is in the ortho- or para-position with respect to the ether oxygen or ether sulphur can be prepared from halonitrobenzones in which the nitro group is in the ortho- or para-position with respect to the halogen and, alkali metal (thio)phenolates in liquid ammonia, the reaction being carried out under pressure and at a temperature from -30° C. to +140° C. and the ammonia being separated off after the reaction is completed.
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- 3-cycloalkyl-prop-2-enamides
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A compound selected from the group consisting of a compound of the formula STR1 wherein R1 is hydrogen or alkyl of 1 to 3 carbon atoms, W is selected from the group consisting of --O--, --S--, --SO-- and --SO2 --, Z and Y are --CH-- or one is --CH-- and the other is --N--, R2, R3, R4, R5 and R6 are individually selected from the group consisting of hydrogen, halogen, methoxy, methylthio, alkyl of 1 to 4 carbon atoms, --WCF3, --CF3, --NO2, --CN--, --W--(CH2)n --CF3, --W--(CF2)n --CF3, --(CF2)n --CF3 and --(CH2)n --CX3, is an integer from 1 to 3, X is a halogen or R3 and R4 together are --O--(CH2)--O-- and R2, R5 and R6 are as defined above, R7 and R8 are individually hydrogen or alkyl of 1 to 6 carbon atoms, R9 is cycloalkyl of 3 to 6 carbon atoms and their non-toxic, pharmaceutically acceptable salts with bases.
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- Phenylcarboxylic acid derivatives
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Phenylcarboxylic acid derivatives having the formula: STR1 wherein R1 and R2 are each H, halogen, alkyl, haloalkyl, alkanoyl, cycloalkyl, nitro, amino, --O--D--R5 (D is alkylene, R5 is H, amino, morpholino, carboxyl, phthalimido, phenyl, epoxy), substituted or unsubstituted phenoxy, substituted or unsubstituted phenylalkylamino, carboxylalkenyl, or both form alkylenedioxy; R3 is H, --E--R6 (E is alkylene, R6 is H, carboxyl, cyano, OH, phenylalkoxy, or halogen-substituted phenyl, or phenylcarbamoyl), --CO--G--R7 (G is alkylene, R7 is H, substituted or unsubstituted phenylcarbamoyl), substituted or unsubstituted benzoyl, alkenyl, carbamoyl, phenyl, or halophenyl; R4 is H or alkyl; A is alkylene, alkylene condensed with cycloalkyl ring, or alkenylene; B is alkylene or alkenylene; l is 0 or 1. Said compounds have fatty acid synthesis-inhibitory activity, cholesterol synthesis-inhibitory activity and are useful as antilipidemic agent, prophylactic and treating agent of artherosclerosis, prophylactic and treating agent of obesity, antidiabetics.
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